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ARTICLE: Jordan D. Metzl, Eric Small, Steven R. Levine, and Jeffrey C. Gershel Creatine Use Among Young Athletes Pediatrics 2001; 108: 421-425 [Abstract] [Full text] [PDF]

P3Rs: Submit a response to this article

P³Rs published:

Creatine Concerns & Link to Steroid Abuse Unfounded

Richard B Kreider   (11 August 2001)

Author Response

Jordan D Metzl   (15 August 2001)

Creatine knowledge to date

Douglas S Kalman   (23 August 2001)

Re: Creatine knowledge to date

Marc Habert   (26 August 2001)

Creatine Concerns & Link to Steroid Abuse Unfounded 11 August 2001
Richard B Kreider, Professor University of Memphis Send letter to journal: Re: Creatine Concerns & Link to Steroid Abuse Unfounded rkreider{at}memphis.edu Richard B Kreider	Dear Editor: I have conducted an extensive amount of research on the safety and efficacy of creatine supplementation and am considered a leading authority in the area. I have no financial interest in creatine or the supplement industry. My interest in creatine has simply been to ascertain the potential ergogenic value and medical safety for athletes and patient populations. I learned about this paper after receiving a call from the Associate Press asking for my interpretation of results. In so doing, I received a copy of this paper and have had an opportunity to thoroughly review the methods, results, and conclusions drawn by these investigators. Although determining whether young athletes use nutritional supplements, pharmacological ergogenic aids, and/or recreational drugs is a valid medical and research question, I was dismayed that Pediatrics would publish such a poorly designed and referenced paper that misrepresents the available scientific and medical literature on creatine as well as draws conclusions that were not supported (or even evaluated) by the research findings. The following describes my primary concerns. 1.) The premise of this paper was that the ergogenic value and safety of creatine supplementation is unknown, particularly in young athletes. In this regard, the authors state “No studies have shown the effectiveness of creatine in people less than 18 years old", "There are no data documenting the safety of creatine in children or adolescents", and "Because creatine has not been studied thoroughly, both the short-term and long-term effects of routine use, especially in adolescents, are of great concern". Although this is a valid research question, the premise is not based on available scientific evidence. While it is true that less is known about the effects of creatine supplementation in younger individuals, short and long-term studies (up to 24 months of ingesting 4-8 grams/d) have in fact been conducted on children (particularly with creatine synthesis deficiencies) and on adolescent athletes (swimmers, football players, etc). Moreover, a number of studies have carefully evaluated the safety and efficacy of creatine supplementation among college athletes (18 - 22 year olds) and other populations. This includes a paper from our lab that reported ergogenic benefit on repetitive swim and sprint performance in junior swimmers ages 12-17 (Int J Sport Nutr. 7(4): 330-46, 1997). A simple literature search would have revealed that the safety and efficacy of creatine supplementation has been evaluated in infants, children, adolescent athletes, young athletes, the elderly, and in various medical populations. I have provided just a brief list of references at the end of this correspondence to illustrate my point. Evidently, the authors of this paper and reviewers were unaware of the over 500 research studies on creatine and creatine analogues as they made the following comment to media “We don't know what this stuff does and we don't know what's in it''. Such comments are simply irresponsible and only serve to mislead the public regarding what we do and don’t know about the efficacy and safety of creatine supplementation. 2.) The study attempted to determine the prevalence of creatine use among young athletes (grades 6-12). The researchers reported that 5.6% of athletes in grades 6-12 (62 of 1103 athletes surveyed) reported taking creatine and that the prevalence of use was higher among males and those in grades 10 – 12. Although this data is of interest, it is not novel in that other recent studies have reported that younger athletes take creatine (as well as other supplements). Moreover, it does not suggest “widespread” use of creatine among young athletes as suggested by the authors but rather limited use among young athletes (particularly in girls and athletes in grades 6-9). Of more concern, I found that the methods employed to obtain these findings were questionable and lacked necessary verification. In this regard, there was no mention that the athletes and their parents gave informed consent to answer this questionnaire. There was no verification that younger athletes really knew what creatine was and/or that their parents confirmed that their children did indeed take creatine (e.g., information on dosage and brands to verify use). There were no questions to ascertain the source of learning about creatine (e.g., friends, family, coaches, trainers, media, Internet, etc), where and how they got creatine (e.g., friends, family, local store, teams, Internet) or whether their parents knew and/or approved of their children taking creatine. Finally, although the authors made bold statements in the article suggesting a link between creatine and steroid use, there was no analysis of steroid use in this population or comparison of use of other nutritional supplements or dangerous substances (alcohol, tobacco, recreational drugs, etc). Consequently, there is no way of putting creatine use in proper perspective to other lifestyle behaviors. For example, how does the incidence of creatine use compare to ingestion of other nutritional supplements (sports drinks, meal replacements, energy bars, weightloss supplements) or known risky behaviors (eating high fat diets/junk food, smoking, drinking alcohol, etc)? Moreover, how do these data compare to behaviors and supplement use among non-athletes? Despite these oversights, these authors made sensational comments to the media like “Not only can creatine use lead to steroid use but, we have no idea whether or not creatine is safe." These conclusions are not supported by the data collected in this study and are clearly irresponsible. 3.) The authors ignored describing the reported clinical benefits of creatine (including in children/adolescents) and misrepresented the literature suggesting that safety of creatine supplementation is unknown. An example of this is the way these authors cite two case reports of renal dysfunction in individuals taking creatine but ignored informing readers of the ten or so clinical trials (not case studies) that have reported that short-term and long-term creatine supplementation (up to 5 years) does not affect renal function. Additionally, the statement “This study confirms the disturbing trend of ergogenic aid use among student athletes" is misleading. The authors cite two papers reporting the incidence of anabolic steroid use among athletes to support this “trend”. Such parallels are inaccurate and misleading. Creatine is not a steroid or a banned pharmacological ergogenic aid. It is an amino acid obtained in the diet and/or synthesized by the body and stored primarily as phosphocreatine in the muscle. All children and adolescent athletes who consume meat and fish ingest creatine every day. Creatine supplementation is simply a convenient way to make sure the body has enough creatine to maintain phosphocreatine levels for high intensity exercise and normal metabolic activity. In my view, creatine has provided a safe and effective nutritional alternative for athletes interested in taking anabolic steroids or prohormones. Creatine supplementation is no different than athletes consuming high carbohydrate foods and/or supplements to maximize glycogen stores and/or load carbohydrate in the muscle. In fact, recent evidence suggests that creatine loading facilitates storage of carbohydrate in the muscle. Water and carbohydrate are also nutritional “ergogenic aids”. Do the authors really believe that “A consistent message of disapproval toward all performance-enhancing substances should come from the medical community“? If so, do they take the same position regarding providing water, sports drinks, or carbohydrate supplements to young athletes? The fact is that there is more long-term safety data on creatine than ingesting sports drinks, carbohydrate loading, or maintaining high carbohydrate diets for athletes. Recommendations about training and nutritional practices for athletes (young or old) should be based on the available scientific and medical evidence, not unsupported speculation. Unfortunately, I found more unfounded speculation in this article than reporting of valuable data. 4.) Finally, what I have found most disturbing about his paper is the sensationalism of results of this study by the authors to the popular media. For example, the lead author has been quoted in the news media (through a PRNews press release from their own institution) that "We don't know what this stuff does and we don't know what's in it'' and "If this study is representative, there are probably over two million American kids and teens taking creatine to give themselves a competitive edge. Not only can creatine use lead to steroid use but, we have no idea whether or not creatine is safe". Such statements are not only unsupported by the results of the study but they misrepresent the scientific and medical literature regarding nutritional ergogenic aids and creatine. Frankly, such comments are irresponsible and reflect poorly on this journal and these researchers. While I do not endorse widespread use of creatine among children and adolescents (see http://www.hmse.memphis.edu/faculty/kreider/NATA/index.html for my position on creatine use among adolescents), I am concerned that this type of sensationalism may misinform physicians, athletes, and parents regarding the safety, potential ergogenic value, and therapeutic uses of creatine. There are numerous reports of potentially beneficial clinical uses of creatine for athletes and various patient populations. The therapeutic role of creatine in a number of medical populations is currently a very active area of research. This report may mislead some physicians and parents to think that no research has been conducted in children or adolescents, that the safety of creatine is completely unknown (in children or adults), and that there is no known ergogenic value of creatine supplementation for this population. Although more research is needed in younger populations, the overwhelming evidence from studies conducted on children, young and older adults, and patients indicates that creatine is safe and generally effective. The fact is there is more evidence that young athletes are at greater medical risk from participating in their sport than taking creatine. Comments and recommendations about creatine should be made on the available scientific evidence, not unsupported speculation so that individuals can base their decision on whether to try creatine or not on the available scientific and medical facts. Respectfully, Richard B. Kreider, PhD, FACSM, EPC Professor & Director Exercise & Sport Nutrition Lab The University of Memphis The following creatine researchers also support my views about the irresponsible nature of this publication and misrepresentation of results of this study to the popular media by this research group. Dr. Theo Wallimann, Prof. Institute for Cell Biology Swiss Federal Institute of Technology Zuerich Zuerich, Switzerland Conrad Earnest, PhD The Cooper Institute Dallas, Texas Mike Greenwood, PhD, CSCS*D Department of Health, Physical Education, and Sport Sciences Arkansas State University Jonesboro, AR Thomas Incledon, MS, RD, LD, LN, CSCS, NSCA-CPT University of Miami Department of Exercise and Sport Science Human Performance Specialists, Inc. Plantation, FL Douglas S. Kalman MS, RD, FACN Director, Nutrition Miami Research Associates Miami, FL Additional References Kamber M. Koster M. Kreis R. Walker G. Boesch C. Hoppeler H. Creatine supplementation--part I: performance, clinical chemistry, and muscle volume. Medicine & Science in Sports & Exercise. 31(12):1763-9, 1999 Dec. Mihic S. MacDonald JR. McKenzie S. Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine & Science in Sports & Exercise. 32(2):291-6, 2000 Feb. Mujika I. Padilla S. Ibanez J. Izquierdo M. Gorostiaga E. Creatine supplementation and sprint performance in soccer players. Medicine & Science in Sports & Exercise. 32(2):518-25, 2000 Feb. Poortmans JR. Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Medicine. 30(3):155-70, 2000 Sep. Robinson TM. Sewell DA. Casey A. Steenge G. Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. British Journal of Sports Medicine. 34(4):284-8, 2000 Aug. Ropero-Miller JD. Paget-Wilkes H. Doering PL. Goldberger BA. Effect of oral creatine supplementation on random urine creatinine, pH, and specific gravity measurements. Clinical Chemistry. 46(2):295-7, 2000 Feb. Schilling BK. Stone MH. Utter A. Kearney JT. Johnson M. Coglianese R. Smith L. O'Bryant HS. Fry AC. Starks M. Keith R. Stone ME. Creatine supplementation and health variables: a retrospective study. Medicine & Science in Sports & Exercise. 33(2):183-8, 2001 Feb. Stoeckler S. Marescau B. De Deyn PP. Trijbels JMF. Hanefeld F. Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 46(10): 1189-93, 1997 Oct. Kreider R. Rasmussen C. Melton C. Greenwood M. Stroud T. Ransom J. Cantler E. Milnor P. Almada A. Long-term creatine supplementation does not adversely affect clinical markers of health. Medicine & Science in Sports & Exercise 32(5 Suppl): S134, 2000 May. Williams, M.H., R.B. Kreider, and D. Branch. Creatine: The Power Supplement. Human Kinetics Publishers, Champaign, IL., 1999, 250 p.
Author Response 15 August 2001
Jordan D Metzl, Sports Medicine Physician Hospital for Special Surgery Send letter to journal: Re: Author Response metzlj{at}hss.edu Jordan D Metzl	August 15, 2001 Dear Dr. Kreider, We have read your letter, submitted on August 9th, concerning our paper "Creatine Use Among Young Athletes" which was published in the August edition of Pediatrics. Your comments are appreciated, as you are a well-known scientist who has produced research concerning the effectiveness of sports supplements. However, we feel strongly that our paper has met the desired objectives, namely to expose the trend in youth sports towards the use of creatine. We believe that we have effectively defined the scope of usage patterns in young athletes in Weschester county. Dr. Kreider, in pediatric medicine, we do not take for granted that results from studies on adults can be extrapolated to growing, developing children and adolescents. For that reason, studies which prove safety and efficacy in adult subjects do not apply to our patients. For example, oxygen is healthy and necessary for adults and children, but causes retinopathy of prematurity in neonates. which can lead to permanent blindness and disability. Although your comments are noted, we stand by our findings, and belive that we have defined creatine usage patterns in young athletes that will stimulate proper research in children and teens. With regard to product-safety, none of the studies that you site has considered young athletes, less than 18 years of age, as primary subjects. We have attempted to review the med line studies that you have listed. Unfortunately, many of the papers which you have referenced are not med line publications and have not been submitted through peer-reviewed journals. Of those we could read, there were no studies that address the long-term safety of this product in children and teens. Dr. Kreider, in clinical medicine, we define long-term safety, not in terms of a product being safe over weeks or months, but over many years. We cite products such as cigarettes, which were initally thought to be healthy, and have subsequently been found to have significantly negative health-effects. In the sports world, only recently Ma Juang, a "safe nutritional supplement", has been implicated as a cause of adverse central nervous system events (NEJM, 2000:343). Although it might be safer alternative to other nutritional suppplements, to not hold creatine to scientific scrutiny before allowing young athletes to take this product is both short-sited and irresponsible. We feel strongly that we have made our case, young athletes are taking creatine, and we need to know more about the safety of this product, both short-term and long-term, before we endorse use in our patients. Sincerely, Jordan D. Metzl, M.D. Eric Small, M.D. Steven R. Levine, M.D. Jeffrey C. Gershell, M.D.
Creatine knowledge to date 23 August 2001
Douglas S Kalman, Scientist Miami Research Associates Send letter to journal: Re: Creatine knowledge to date dkalman{at}miamiresearch.com Douglas S Kalman	Dear Editor, We read with great interest the recent article regarding creatine use among young athletes by Metzl et al (1). It is unfortunate that these fine clinicians have sensationalized a topic of interest through interviews with the Associated Press, while not reporting what is currently known regarding the safety and efficacy of creatine monohydrate supplementation. We do applaud Metzl and colleagues for indicating that younger and adolescent athletes should first aim to train smart, eat healthy and get adequate rest in order to enhance performance but are dismayed by their lack of knowledge regarding the safety and efficacy of creatine in both medical therapeutics and sporting uses. Metzl and colleagues recently replied to a letter to the editor posted by one of the most published creatine researchers in the United States (Richard Kreider, Ph.D., FACSM) not by citing accurate research to support their claims, but by resorting to physician snobbery (“Dr. Kreider, in clinical medicine we…”). This was magnified by their claiming they could not find any of the 10 plus references cited by Dr. Kreider on Medline. All of these studies can be found on www.ncbi.nlm.nih.gov/PubMed or other similar search engines. Knowing this, and the ease of attending physicians (within teaching hospital systems) being able to request/obtain articles from the medical library, one is compelled to believe that Metzl et al were more interested in headlines rather than what science currently exists regarding the safety and efficacy of creatine in young athletes. We do not endorse the use of creatine in young athletes. Rather, we are stating that being ignorant of/ignoring the controlled studies that do demonstrate the safety and efficacy of creatine is no excuse for linking them to the possible side effects associated with anabolic steroids. In terms of the safety of long term use of creatine, studies reporting on five years use of creatine (in healthy college aged men and women) indicate no untoward effects in both clinical chemistries and subjective complaint (2). Despite the common association of creatine with renal impairment (likely because of confusion with creatinine, a marker of renal function and the irreversible cyclization product of creatine), several studies have shown no adverse impact upon renal function (5-7). There are also data concerning the short and long-term therapeutic benefit of creatine supplementation in children and adults with gyrate atrophy (a result of the inborn error of metabolism with ornithine delta- aminotransferase activity), guanidinoacetate methyltransferase deficiency (GAMT, an inborn error of metabolism), muscular dystrophy (facioscapulohumeral dystrophy, Becker dystrophy, Duchenne dystrophy and sarcoglycan deficient limb girdle muscular dystrophy), McArdle’s disease, Huntington’s disease, hypercholesterolemia, amyotrophic lateral sclerosis, and now both Type I and II diabetes (creatine is a guanidino based compound as is the prescription hypoglycemic agent, metformin, a biguanide) (8-25). As sports medicine physicians, we would not expect Metzl et al to be aware of the therapeutic uses of creatine in children and adults. However, many of these studies have involved treatment of children with various diseases and have been published in pediatric medicine journals. Additionally, as researchers, they should be aware of all available data regarding the safety and efficacy of creatine supplementation before making misinformative statements in their article and to the press. In terms of the uses of creatine in young athletes (adolescents), Metzl et al correctly point out that one can not extract safety data from the adult population and apply it to the younger members of our society. However, there are over 30 available studies examining the safety and/or efficacy of creatine in youths (infants through 19 years of age), ingesting chronic daily doses (up to 670 mg/kg body weight) that are greater than double the adult daily loading dose. The studies range in duration from a few weeks to five or more years of creatine usage (2-19). None indicate any serious or even mild adverse events and most report improved clinical outcomes. As pointed out above, many published studies and recent abstracts (26-63) have examined the safety of creatine in young college aged athletes (often 18-19 years of age). Furthermore it is with great disrespect to the youth for Metzl et al to state that “creatine use in youth may lead to anabolic-androgenic steroid (AAS) use”. It is estimated that illegal drug and alcohol abuse is of greater concern in the youth, since 14.6% of eighth graders, 23.2% of tenth graders and 24.6% of twelfth graders report using an illicit drug (64). On the other hand, 5.6% use of creatine in adolescents is not wide spread; it is simply six out of every hundred people sampled. As pediatric medicine appears to be the focus of Metzl’s work, the cause for concern is that 59.95% of males and 40.1% of females reported partaking in sports while under the influence of alcohol or illicit drugs (65). Creatine is not a drug, nor is it a gateway drug. We know that alcohol and illicit drug use can produce severe, even fatal “adverse effects” and that they are gateway drugs. Creatine is ingested daily in the American diet in the form of meats and other animal-derived foods, and there are no data to support the notion that taking a nutritional supplement leads to drug abuse. Moreover, we assert that because creatine is a dietary supplement it incurs far more rigorous scrutiny, often crafted with a “double standard” tone: case reports are cited and often waved as victory flags documenting toxicity yet the abundant randomized controlled trials are either pilloried as being “short term” or “inconclusive”. What prevents clinicians such as Metzl and his colleagues from investigating youth perceptions regarding artificial sweeteners e.g. sucralose, which has a complete lack of published safety studies of any length in pre-teen/early teen populations (Medline search performed August 21, 2001)? Surely the sheer number of youth consumers ingesting sucralose- sweetened beverages, coupled with the foreign, non-native chemistry of this sweetener, raises long-term safety concerns. In summary, we do agree that more research is needed exploring the potential role of creatine as a therapeutic aid for various medical conditions and in the youth. We do not recommend creatine supplementation in people less than 18 years of age, however it should be acknowledged that peer-reviewed research does indicate that approximately 70% of all studies examining its potential ergogenic capability demonstrate a positive effect. Outside of the very limited number of case studies, no data indicates creatine supplementation to be harmful in healthy, normal people. We hope that Metzl et al will consider this scientific dialogue an attempt to disclose the entire body of scientific literature on creatine, presenting a more balanced and honest discussion of the topic to your readership. As scientists and clinicians, it is our view that hypotheses should be tested through controlled research and statements made about ones research should be based on the data observed rather than speculation not supported by their data. Sincerely, Douglas S. Kalman MS, RD, FACN Director, Clinical Nutrition Miami Research Associates 6280 Sunset Drive Suite 600 Miami, FL 33143 305-666-2368 www.miamiresearch.com Thomas Incledon, MS, RD, CSCS Human Performance Specialists, Inc. and University of Miami, Department of Exercise and Sport Science Michael Greenwood, PhD, CSCS *D Associate Professor & Graduate Coordinator Human Performance Laboratory, Arkansas State University Susan M. Kleiner, Ph.D., RD High Performance Nutrition 7683 SE 27th Street, #167 Mercer Island, WA 98040 ph. 206-232-9138 fax 206-236-2188 Richard B. Kreider, PhD, FACSM, EPC Professor and Director Exercise & Sport Nutrition Lab The University of Memphis Jacques R. Poortmans, Ph.D., FACSM, Professor, Chimie Physiologique,- ISEPK Universite Libre de Bruxelles (Belgium), 28 Av. P. Heger B-1000 Bruxelles Tel : 32-2-650.2195 Fax : 32-2-650.4209 E-mail : jrpoortm@ulb.ac.be Anthony L. Almada MSc President ImagiNutrition/MetaResponse Sciences 30131 Town Center Drive Suite 211 Laguna Niquel, CA 92677 Mike Stone Ph.D., CSCS Chair of Sport Edinburg University Edinburg, Scotland References: 1) Metzl, JD, Small E, Levine SR. Creatine use among young athletes. Pediatrics 2001;108:421-425. 2) Schilling BK, Stone MH, Utter A, et al. Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc 2001;33(2):183-188. 3) Stone MH, Sanborn K, Smith LL, O'Bryant HS, Hoke T, Utter AC, Johnson RL, Boros R, Hruby J, Pierce KC, Stone ME, Garner B. Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999 Jun;9(2):146-65. 4) Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000 Sep;30(3):155-70. 5) Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999 Aug;31(8):1108-10. 6) Ropero-Miller J D, Paget-Wilkes H, Doering Pl, Goldberger BA. Effect of oral creatine supplementation on random urine creatinine, pH, and specific gravity measurements. Clin Chem 2000 46(2): 295-297. 7) Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 2000 34(4): 284-288. 8) Vannas-Sulonen K, Sipala I, Vannas A, et al. Gyrate atrophy of the choroids and retina: A five year follow-up of creatine supplementation. Ophthamology 1985;92:1719-1727. 9) Heinanen K, Nanto-Salonen K, Komu M, et al. Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. Eur Clin Invest 1999;29(12):1060-1065. 10) Stockler S, Marescau B, De Deyn PP, et al. Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 1997;46(10):1189-1193. 11) Stockler S, Hanefeld F, Frahm J. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 1996 Sep 21;348(9030):789-90. 12) Stockler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K. Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 1996 May;58(5):914-22. 13) Stockler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hanicke W, Frahm J. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 1994 Sep;36(3):409-13. 14) Schulze A, Hess T, Wevers R, Mayatepek E, Bachert P, Marescau B, Knopp MV, De Deyn PP, Bremer HJ, Rating D. Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. J Pediatr 1997 Oct;131(4):626-31. 15) Leuzzi V, Bianchi MC, Tosetti M, Carducci C, Cerquiglini CA, Cioni G, Antonozzi I. Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). Neurology 2000 Nov 14;55(9):1407-9. 16) Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, Bruns N, Fabian K, Tegenthoff M, Mortier W, Luttmann A, Zange J, Malin JP. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Arch Neurol 2000 Jul;57(7):956-63. 17) Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Neurol Res 2000 Mar;22(2):145- 50. 18) Valtonen M, Nanto-Salonen K, Jaaskelainen S, Heinanen K, Alanen A, Heinonen OJ, Lundbom N, Erkintalo M, Simell O. Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia. J Inherit Metab Dis 1999 Dec;22(8):855-66. 19) Borchert A, Wilichowski E, Hanefeld F. Supplementation with creatine monohydrate in children with mitochondrial encephalomyopathies. Muscle Nerve 1999 Sep;22(9):1299-300. 20) Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA. Guanidinoacetate methyltransferase deficiency: new clinical features. Pediatr Neurol 1997 Sep;17(2):155-7. 21) Schulze E, Mayatepek P, Bachert B, Marescau PP, De Deyn D. Therapeutic trial of arginine restriction in creatine deficiency syndrome. Eur J Pediatr 1998;157: 606-607. 22) Earnest C, Almada A, Mitchell T. High performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci 1996;91:113-118. 23) Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 2000;20(12):4389-4397. 24) Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double blind, placebo-controlled clinical study. Neurology 2000;54(9):1848-1850. 25) Lipovac V, Gavella M, Vucic M, et al. Effect of creatine on erythrocyte rheology in vitro. Clin Hemorheol Microcirc 2000;22(1):45-52. 26) Larsen SD, Connell MA, Cudahy MM, et al. Synthesis and biological activity of analogues of the antidiabetic/antiobesity agent agent 3- guanidinopropionic acid: discovery of a novel aminoguanidinoacetic acid antidiabetic agent. J Med Chem 2001;44(8):1217-1230. 27) Bajuk NB. Therapeutic comparison of metformin and creatine in the glycemic control of patients with Type II diabetes. Diabetes 2001;30 (supplement 2):1793-PO. 28) Smith J, Dahm DL. Creatine use among a select population of high school athletes. Mayo Clin Proc 2000;75(12):1257-1263. 29) Kreider, R.B., C. Rasmussen, J. Ransom, and A.L. Almada. Effects of creatine supplementation during training on incidence of muscle cramping, injuries, and GI distress. J Str Cond Res. 1998;12:275. 30) Kreider, R., J. Ransom, C. Rasmussen, J. Hunt, C. Melton, T. Stroud, E. Cantler & P. Milnor. Creatine supplementation during preseason football training does not affect markers of renal function. FASEB J. 1999;13: A543,. 31) Melton, C., R. Kreider, C. Rasmussen, J. Ransom, J. Hunt, T. Stroud, E. Cantler & P. Milnor. Effects of ingesting creatine-containing supplements during training on blood lipid profiles. FASEB J. 1999;13: A559. 32) Kreider, R., C. Melton, J. Hunt, C. Rasmussen, J. Ransom, T. Stroud, E. Cantler & P. Milnor. Creatine does not increase incidence of cramping or injury during preseason college football training I. Med Sci Sport Exer. 1999;31(5): S355. 33) Hunt, J., R. Kreider, C. Melton, J. Ransom, C. Rasmussen, T. Stroud, E. Cantler & P. Milnor. Creatine does not increase incidence of cramping or injury during preseason college football training II. Med Sci Sport Exer. 1999;31(5): S355. 34) Rasmussen, C., R. Kreider, J. Ransom, J. Hunt, C. Melton, T. Stroud, E. Cantler & P. Milnor. Creatine supplementation during preseason football training does not affect fluid or electrolyte status. Med Sci Sport Exerc. 1999;31(5): S299. 35) Ransom, J., R. Kreider, J. Hunt, C. Melton, C. Rasmussen, T. Stroud, E. Cantler & P. Milnor. Effects of creatine supplementation during training on markers of catabolism and muscle & liver enzymes. Med Sci Sport Exerc. 1999;31(5): S265. 36) Kreider, R., C. Melton, J. Ransom, C. Rasmussen, T. Stroud, E. Cantler, M. Greenwood & P. Milnor. Creatine Supplementation does not increase incidence of cramping or injury during college football training I. J Str Cond Res. 1999;13:428. 37) Greenwood, M., R. Kreider, J. Ransom, C. Rasmussen, C. Melton, T. Stroud, E. Cantler, & P. Milnor. Creatine Supplementation does not increase incidence of cramping or injury during college football training II. J Str Cond Res. 1999;13: 425-426. 38) Ransom, J., R. Kreider, C. Rasmussen, C. Melton, T. Stroud, E. Cantler, M. Greenwood & P. Milnor. Effects of long-term creatine supplementation during training on markers of catabolism and enzyme efflux J Str Cond Res. 1999;13: 429. 39) Rasmussen, C., R. Kreider, C. Melton, J. Ransom, T. Stroud, E. Cantler, M. Greenwood & P. Milnor. Long?term creatine supplementation during football training does not affect markers of renal stress. J Str Cond Res. 1999;13: 431. 40) Melton, C., R. Kreider, C. Rasmussen, J. Ransom, T. Stroud, E. Cantler, M. Greenwood & P. Milnor. 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Re: Creatine knowledge to date 26 August 2001
Marc Habert, Pediatrician Children's Medical Group Send letter to journal: Re: Re: Creatine knowledge to date marcohaber{at}aol.com Marc Habert	As a practicing pediatrician, I speak with 3-4 adolescents a day (ages ranging from 13-16) about creatine use. These mostly male athletes want to know if they should use creatine. They have friends who use them and most would like to increase muscle bulk. I was pleased that this article was published...and I was pleased at the attention the national media paid this article. It seems to me that the safety of creatine supplementation in adolescents is still a very much open question. I do not think that you can generalize studies in which children with certain metabolic problems took creatine to healthy adolescents. In looking at the articles cited that are supposed to show efficacy and safety of creatine, these are not done on the population that I deal with...namely 13-16 year old healthy adolescents. I thank Dr. Metzl for this descriptive study as well as the publicity that this generated.

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